DESCRIPTION: It is hypothesized that cancer cells are less able than normal cells to tolerate oxidative stress. The applicants provide evidence that preexposure of cancer and normal cells to n-3 polyunsaturated fatty acids increases the amount of oxidizable substrate in cellular membranes, effectively presensitizing cancer cells to oxidizing abilities of chemotherapeutic drugs. Normal cells are better able to produce antioxidants than cancer cells and thus are better protected against oxidation. The result is selective death of cancer cells and increased efficacy of chemotherapeutics. The project will test the above hypothesis by addressing the following specific aims: 1. Pretreatment of cancer and normal cells with n-3 fatty acids followed by cytotoxic chemotherapeutic agents in the presence and absence of supplemental iron to demonstrate preferentially enhanced cytotoxicity; 2. Feed n-3 fatty acids to nude mice bearing MDA-MB 231 human breast tumors with n-3 fatty acids in the presence and absence of supplemental iron to enhance therapeutic efficacy and without enhancing drug induced toxicity; and 3. Compare in vitro and in vivo cell culture conditions for use as a potential rapid throughput screening model for combinatorial effects of n-3 fatty acids, iron and cytotoxic chemotherapeutic agents. In Phase II, clinical trials to validate human efficacy will be proposed in addition to the development of proprietary, clinically useful n-3 fatty acid formulations. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE